Gene Segregation and Interaction Lecture Notes PDF

III. Gene Segregation and Interaction A. Law of Segregation Mendel’s Law of Segregation describes how alleles for a single trait separate during gamete formation Each gamete receives only one allele from each gene pair, ensuring that offspring inherit one allele from each parent A. Law of...

III. Gene Segregation and Interaction A. Law of Segregation Mendel’s Law of Segregation describes how alleles for a single trait separate during gamete formation Each gamete receives only one allele from each gene pair, ensuring that offspring inherit one allele from each parent A. Law of Segregation Key Observations from Mendel's Experiments: 1. Each organism carries two alleles for each trait 2. Alleles segregate during gamete formation (meiosis) 3. During fertilization, alleles recombine to form the genotype of the offspring Monohybrid Cross: - Parental generation: RR (round seeds) × rr (wrinkled seeds) - F1 generation: All Rr (round seeds) - F2 generation (self-fertilization): 3:1 phenotypic ratio (round: wrinkled) B. Law of Independent Assortment Mendel's Law of Independent Assortment states that the alleles of different genes segregate independently of one another during gamete formation Dihybrid Cross: - Parents: RRYY (round yellow) × rryy (wrinkled green) - F1 generation: All RrYy (round yellow) - F2 generation: 9:3:3:1 phenotypic ratio (round yellow: round green: wrinkled yellow: wrinkled green) C. Chromosomal Basis of Mendelian Laws Mendel’s laws were later explained by the behavior of chromosomes during meiosis Segregation: Homologous chromosomes (and their associated alleles) separate during meiosis I Independent Assortment: Chromosomes carrying different genes assort independently when forming gametes, leading to varied genetic combinations D. Dominance Relationships 1. Incomplete Dominance (No Dominance) 2. Overdominance 3. Co-Dominance D. Dominance Relationships 1. Incomplete Dominance (No Dominance) The heterozygous phenotype is an intermediate between the two homozygous phenotypes Example: In Mirabilis jalapa (four o'clock plant), crossing red (RR) and white (rr) flowers produces pink (Rr) flowers F2 ratio: 1 red : 2 pink : 1 white D. Dominance Relationships 2. Overdominance The heterozygote has a superior or more exaggerated phenotype than either homozygote Example: In Drosophila, the heterozygote (w*/w) produces more fluorescent pigments than the homozygous wild type (w*/w*) or mutant (w/w) D. Dominance Relationships 3. Co-Dominance Both alleles in a heterozygote are fully and equally expressed Example: In MN blood groups, a heterozygote (MN) expresses both M and N antigens equally on red blood cells E. Multiple Alleles When more than two alleles exist for a gene in a population Example: ABO blood group in humans, which has three alleles (A, B, O) E. Multiple Alleles Isoalleles: Alleles that have similar phenotypic effects Mutant Isoalleles: Produce a variation from the normal phenotype Normal Isoalleles: Produce the typical phenotype F. Lethal Genes 1. Recessive Lethals Lethal when in the homozygous recessive condition Example: Tay-Sachs disease in humans (homozygous individuals die in infancy) F. Lethal Genes 2. Dominant Lethals Lethal in both the homozygous and heterozygous state Example: Huntington’s disease, where symptoms manifest later in life and cause death in heterozygous individuals F. Lethal Genes 3. Penetrance of Lethal Genes Describes the extent to which a lethal gene is expressed Some lethal genes are semi-lethal, meaning a portion of affected individuals survive 4. Environmental Influence on Lethal Genes Conditional Lethal: Lethal only under specific environmental conditions Example: Temperature-sensitive lethal mutations in Drosophila that are lethal at restrictive temperatures but survivable at permissive temperatures G. Modifier Genes Modifiers: Genes that change the phenotypic effects of other genes in a quantitative fashion Enhancement: Increases the effect of the main gene Dilution: Reduces the effect of the main gene Suppressors: Modifiers that mask or completely suppress the expression of mutant alleles  Dilution: Reduces G. Modifier Genes the effect of the main gene H. Gene Interactions Gene interactions often result in phenotypic ratios that deviate from Mendelian expectations These interactions occur when two or more genes influence a single trait 1. Novel Phenotypes 2. Recessive Epistasis 3. Dominant Epistasis 4. Complementary Genes 5. Duplicate Genes  1. Novel Phenotypes Interaction between alleles produces new H. Gene Interactions phenotypes Example: Comb shape in chickens, where the interaction of two genes results in four phenotypes (walnut, rose, pea, single) H. Gene Interactions 2. Recessive Epistasis A recessive allele at one gene locus masks the effects of another gene Example: Coat color in mice (9:3:4 ratio), where the cc genotype results in albinism regardless of the other gene’s allele  3. Dominant Epistasis H. Gene Interactions a. In summer squash, a dominant allele (W) masks the expression of another gene (Y) for color (12:3:1 ratio) H. Gene Interactions 3. Dominant Epistasis b. In fowl feather color, dominant inhibitors prevent color expression, producing a 13:3 phenotypic ratio H. Gene Interactions 4. Complementary Genes Two genes must both have dominant alleles for a particular phenotype to be expressed Example: Flower color in peas, where both genes are necessary to produce purple flowers (9:7 ratio) H. Gene Interactions 5. Duplicate Genes Either of two genes can produce the same phenotype Example: Seed capsule shape in Shepherd’s purse (15:1 ratio) I. Pseudoalleles Example: The Star-asteroid case in Drosophila, where recombination between closely linked genes produces new phenotypes This phenomenon, known as the Lewis Effect or Position Effect, indicates that phenotype is influenced by both genotype and allele position on the chromosome J. Environmental Influence on Gene Expression The environment can significantly influence gene expression and the resulting phenotype 1. Penetrance 2. Expressivity 3. Pleiotropy 4. Phenocopy J. Environmental Influence on Gene Expression 1. Penetrance Penetrance refers to the proportion of individuals with a specific genotype that express the expected phenotype Example: Some individuals with a dominant allele for polydactyly (extra fingers) may NOT express the trait, a phenomenon called incomplete penetrance J. Environmental Influence on Gene Expression 2. Expressivity Expressivity refers to the degree to which a genotype is expressed in individuals with the same genotype Example: In people with polydactyly, the extra digit may vary in size J. Environmental Influence on Gene Expression 3. Pleiotropy Pleiotropy occurs when a single gene affects multiple traits Example: The gene for phenylketonuria (PKU) affects multiple body systems, including brain development and skin pigmentation J. Environmental Influence on Gene Expression 4. Phenocopy A phenocopy occurs when an environmental condition mimics a genetic phenotype Example: Exposure to thalidomide during pregnancy can cause limb malformations like that of genetic conditions J. Environmental Influence on Gene Expression External Environmental Factors Temperature: Coat color in Siamese cats and Himalayan rabbits is influenced by temperature, with cooler body parts producing darker fur J. Environmental Influence on Gene Expression External Environmental Factors Light: Plants need light for chlorophyll production, and the intensity of light can affect growth patterns J. Environmental Influence on Gene Expression External Environmental Factors Nutrition: Nutritional factors can influence the expression of certain genes J. Environmental Influence on Gene Expression External Environmental Factors Maternal Relations: Blood type incompatibilities between mother and fetus can affect fetal survival J. Environmental Influence on Gene Expression Internal Environmental Factors Age: Some genetic traits manifest only later in life, such as baldness or Huntington's disease J. Environmental Influence on Gene Expression Internal Environmental Factors Sex: Traits such as milk production are limited to one sex J. Environmental Influence on Gene Expression Internal Environmental Factors Substrates: The reactions in an organism largely depend on the substrates it synthesizes, which may be genetically controlled K. Twin Studies Twin studies help distinguish between the effects of genetics and the environment by comparing traits between identical (monozygotic) and fraternal (dizygotic) twins Concordant: Twins share the same trait Discordant: One twin expresses the trait, and the other does not  The extent of twin concordance can measure the roles of environment and heredity in expressing a phenotype L. Probability and Statistical Testing 1. Product Law The probability of two independent events occurring together is the product of their individual probabilities Example: In a dihybrid cross, the probability of getting round yellow seeds is 9/16 2. Sum Law The probability of one of two mutually exclusive events occurring is the sum of their probabilities Example: The probability of getting either a dominant or recessive allele for a trait is the sum of their probabilities L. Probability and Statistical Testing 3. Level of Significance The degree to which the observed data differ from the expected results can be assessed through statistical significance testing 4. The Chi-Square Test A statistical method used to compare observed genetic ratios with expected ratios Formula: χ² = Σ (O - E)² / E L. Probability and Statistical Testing 5. Binomial Distributions Used to calculate the probability of specific combinations of genotypes appearing in offspring 6. Normal Distribution As sample sizes increase, the distribution of genetic traits in a population follows a bell-shaped curve IV. LINKAGE AND RECOMBINATION INTRODUCTION Genes located on different chromosomes are not linked This allows independent assortment – in a di-hybrid cross the traits show the classic 9:3:3:1 inheritance pattern INTRODUCTION The number of genes in an organism far exceeds the number of chromosomes A single chromosome bears several genes Is independent assortment always the case? No Independent assortment states that during gamete formation, the two alleles for one gene segregate or assort independently of the alleles for other genes But if two genes are found on the same chromosome, they will not assort independently, and do not follow Mendelian inheritance patterns Genes that are inherited together are said to be “linked” LINKAGE Linked genes: Genes present at the same locus that have the tendency to be linked together from one generation to the other and are not disturbed by the meiotic recombination Linkage is defined as “the tendency of genes to remain together during the process of inheritance” LINKAGE When two loci are linked genetically on the same chromosome, they do not segregate Extent of linkage: the closer the genes, the stronger the linkage and vice versa Linkage of genes is in the linear fashion in the chromosomes  The genes that show linkage are located on the same chromosome A linkage group is formed by all the linked genes in a chromosome The strength of linkage between two genes is directly proportional to the distance between them  THE DISCOVERY OF GENETIC LINKAGE William Bateson and Reginald Punnett completed a study in 1905 that determined the movement of alleles found on the same chromosome The study used sweet peas, particularly flower color and pollen shape; they followed the inheritance pattern THE DISCOVERY OF GENETIC LINKAGE For flower color, purple (P) is dominant over red (p), and for pollen shape long (L) is dominant over round (l) A cross was performed using a true breeding purple/long (PPLL) and red/round (ppll): PPLL x ppll The F1 generation was 100% purple/long (PpLl) THE DISCOVERY OF GENETIC LINKAGE Crossing two individuals from the F1 generation resulted in an F2 generation with four different phenotypes (purple/long, purple/round, red/long and red/round) The alleles that created these combinations did NOT follow the 9:3:3:1 pattern, and supported the idea that these alleles did not assort independently and therefore must be linked WHY LINKAGE Linkage refers to the packaging of genes in chromosomes Chromosomes, and therefore linkage, are for organizing genes for their safe coordinated transmission from cell to cell (parent to offspring) TYPES OF LINKAGE Depending upon the presence or absence of new combinations or non-parental combinations, linkage can be of two types: i. Complete Linkage If two or more characters are inherited together and consistently appear in two or more generations in their original or parental combinations, it is called complete linkage These genes do not produce non-parental combinations TYPES OF LINKAGE i. Complete Linkage When two or more genes tend to remain together on the same chromosome and are inherited together for many generations Happens when chromosomes do NOT undergo any breakage by accident during gametogenesis i.e., They may be so close to each other that they cannot be separated by recombination during meiosis TYPES OF LINKAGE ii. Incomplete Linkage Incomplete linkage is exhibited by those genes which produce some percentage of non-parental combinations Such genes are located distantly on the chromosome It is due to accidental or occasional breakage of chromosomal segments during crossing over TYPES OF LINKAGE ii. Incomplete Linkage When the linked genes tend to separate on some occasions during inheritance Occurs in the process of crossing over during gametogenesis i.e., Genes located far apart on the same chromosome typically show incomplete (partial) linkage because they are easily separated by recombination SIGNIFICANCE OF LINKAGE 1. Linkage does not permit the breeders to bring the desirable characters in one variety. For this reason, plant and animal breeders find it difficult to combine various characters. 2. Linkage reduces the chance of recombination of genes and thus helps to hold parental characteristics together. It thus helps organism to maintain its parental, racial and other characters. AUTOSOMAL & SEX LINKAGE Autosomal linkage: the linked genes are present on the autosomes Sex linkage: the linked genes are present on the sex chromosomes SEX LINKAGE Linkage groups in guppy detected by Winge (1923) Almost all the genes involved in color pigmentation and patterning are sex-linked The first species shown to have Y-linked inheritance of genes CROSSING-OVER AND THE INHERITANCE OF LINKED GENES Linked genes do NOT always stay linked These linkage groups can be separated by crossing-over during prophase I of meiosis Linked genes are NOT inherited together every time chromosomes exchange homologous genes during meiosis  CROSSING-OVER AND THE INHERITANCE OF LINKED GENES When crossing over occurs, the genes that were previously linked become unlinked, creating four different types of chromosomes (gametes) The proportions are NOT equal because crossing over does NOT occur in every cell during meiosis CROSSING-OVER The physical exchange of DNA between two non-sister chromatids of homologous chromosomes following synapsis at meiosis Results in the recombination of genetic material CROSSING-OVER 1, 2 or more fragments may be interchanged during crossing-over Prevalence of recombination is dependent on the distance between linked genes PARENTAL GAMETES AND RECOMBINANT GAMETES Parental gametes are the gametes that maintain the original linkage of genes (alleles) in the chromosome Recombinant gametes are those in which the original linkage is undone due to exchange of chromosomal pieces via crossing-over during meiosis SIGNIFICANCE OF CROSSING-OVER Produces new combinations of traits Through crossing over, segments of homologous chromosomes are interchanged and hence provide origin of new characters and genetic variations Crossing over plays a very important role in the field of breeding to improve the varieties of plants and animals THEORIES OF CROSSING-OVER i. Contact-First Theory : The inner two chromatids of the homologous chromosomes first touch each other and then cross over. At the point of contact, breakage occurs. The broken segments again unite to form new combinations. THEORIES OF CROSSING-OVER ii. The Breakage-First Theory : The chromatids first break into two without any crossing over, and after that, the broken segments reunite to form the new combinations. CROSSING-OVER Frequency of crossing-over of a given pair of genes is not constant Temperature, nutrition, sex, age, etc. influence crossing-over Crossing over frequencies are higher in the female sex than in males Brings about variation and leads to evolution through natural selection FACTORS AFFECTING CROSSING-OVER 1. Sex: there is a tendency of reduction of crossing over in male mammals 2. Mutation: mutation reduces crossing over 3. Temperature: high and low temperature variations increase the percentage of crossing over in certain parts of the chromosome 4. X-ray Effect: X-ray irradiations increase crossing over near centromere 5. Age: older age increases the rate of crossing over TYPES OF CROSSING-OVER i. Single Crossing-Over: Only one chromatid of each chromosome is involved in single crossing-over, and only one chiasma is formed all along the length of a chromosome pair Gametes formed by this type of crossing-over are called single cross-over gametes Single crossing-over is of most frequent occurrence TYPES OF CROSSING-OVER ii. Double Crossing-Over: Two, three or all four chromatids of the homologous pairs of chromosomes are involved in the process of double crossing-over Two chiasmata are formed along the entire length of the chromosome The chiasmata may be between the same chromatids or between different chromatids TYPES OF CROSSING-OVER ii. Double Crossing-Over: Double cross-over gametes are produced This is of less frequent occurrence TYPES OF CROSSING-OVER iii. Multiple Crossing-Over: Crossing-over occurs at more than two points on the same chromosome pair, and more than two chiasmata are formed Corresponding to the number of chiasmata formed, it is called triple (3 chiasmata), quadruple (4 chiasmata), and so on It is a rare phenomenon CROSSING-OVER Provides a direct evidence of the linear arrangement of genes in the chromosomes Chromosome maps can be constructed Gives rise to new combinations of genes, hence variations in offspring CHROMOSOME MAPPING Sturtevant (1913) constructed the first chromosome map showing the position genes on the X chromosome Genetic maps of chromosomes are also known as chromosome maps GENE MAPPING Refers to the analysis of loci on the genome revealing the linear order of different genes on the chromosomes Two types of gene maps: 1) Physical maps 2) Genetic maps PHYSICAL MAPS Based on the assignment of loci to chromosomes Accomplished by the methods 1) somatic cell hybrid panels 2) in situ hybridization 3) comparative mapping PHYSICAL MAPS In physical maps, the coordinates are the chromosome regions or bands The distance between two loci are measured in kilobases GENETIC MAPS Constructed by studying the meiotic recombination between two or more loci through linkage analysis Do not provide an absolute location of loci but they reveal the genetic distance of the loci as a function of the frequency of crossing-overs occurring during recombination Provides an ordered array or sequence tagged sites along the chromosome GENETIC DISTANCE Expressed in units of crossing over or centimorgan (cM) One cM equals 1% crossing over and contains approximately 1000 kb i.e., Two loci which show 1% recombination are 1 cM apart on a genetic map GENETIC DISTANCE In a linkage, a new locus is assigned based on an already known locus It shows that a reference locus is a prerequisite for the purpose MAP UNIT One map unit is defined as the linkage distance that yields 1% recombination LINKAGE GROUP When many genes are mapped in any given species, the genes are observed to occur in linkage groups, with one linkage group corresponding to each pair of chromosomes FISH (Fluorescent In Situ Hybridization) Highly effective, rapid technique for use in gene mapping Probes are labeled with fluorochrome dyes which fluoresce in different colors when excited by UV–light Location of the probes are visualized under Epifluoresence microscope CHROMOSOME PAINTING It is one of the applications of FISH techniques Whole chromosomes specific probes are called paints CHROMOSOME PAINTING The direct visualization of specific chromosomes by fluorescent detection by hybridized labeled whole chromosome probes is called chromosome painting CHROMOSOME PAINTING Used to improve the accuracy of cytogenetic studies, closing the gap between cytogenetic and molecular analysis Used in the identification of species-specific chromosomes among somatic cell hybrids Used in the detection of Chromosomal rearrangements or abnormalities for which no locus–specific probes are available RECAP Linkage It is tendency of genes on a chromosome to remain together and passed as such in next generation It brings more parental types Strength of linkage between two genes increases if they are closely placed on a chromosome It helps to maintain a newly improved variety RECAP Crossing-over It is exchange of genes or chromosomal parts to break established linkage and formation of new linkage It produces recombination Frequency of crossing-over between two genes decreases if they are closely placed It is the source of variation for producing new varieties